BST1 protein (Bone Marrow Stromal Cell Antigen 1, also known as CD157 or ADP-ribosyl cyclase 2) is a GPI-anchored cell surface enzyme encoded by the [BST1](/genes/bst1) gene. BST1 catalyzes the synthesis of cyclic ADP-ribose (cADPR) from NAD+, regulating intracellular calcium signaling. BST1 is expressed on immune cells, bone marrow stromal cells, and within the central nervous system. Genome-wide association studies have identified BST1 as a significant risk locus for [Parkinson's disease](/diseases/parkinsons-disease), with risk variants potentially affecting microglial immune function and calcium homeostasis in the brain.
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BST1 Protein
Overview
BST1 protein (Bone Marrow Stromal Cell Antigen 1, also known as CD157 or ADP-ribosyl cyclase 2) is a GPI-anchored cell surface enzyme encoded by the [BST1](/genes/bst1) gene. BST1 catalyzes the synthesis of cyclic ADP-ribose (cADPR) from NAD+, regulating intracellular calcium signaling. BST1 is expressed on immune cells, bone marrow stromal cells, and within the central nervous system. Genome-wide association studies have identified BST1 as a significant risk locus for [Parkinson's disease](/diseases/parkinsons-disease), with risk variants potentially affecting microglial immune function and calcium homeostasis in the brain.
NAD+ binding: NAD+ enters the active site cleft; BST1 cleaves the nicotinamide-ribose bond and cyclizes ADP-ribose to form cADPR
Compared to CD38: BST1 has weaker cyclase activity but stronger NADase (hydrolase) activity, producing ADPR as the major product
GPI Anchor and Lipid Raft Association
The GPI anchor tethers BST1 to the outer leaflet of the plasma membrane
BST1 partitions into cholesterol-rich lipid raft microdomains
Lipid raft localization is important for signal transduction and receptor clustering
BST1 can be released from the cell surface by GPI-specific phospholipase C or shed by metalloproteinases
Normal Function
NAD+ Metabolism and Calcium Signaling
BST1 catalyzes the conversion of NAD+ to cyclic ADP-ribose (cADPR):
cADPR activates ryanodine receptors on the ER, releasing intracellular Ca2+
This NAD+-calcium signaling axis regulates cell activation, proliferation, and chemotaxis
BST1 also generates ADPR, which activates TRPM2 calcium channels
In [neurons](/entities/neurons), cADPR/ADPR signaling modulates synaptic transmission and plasticity
Immune Cell Functions
Neutrophil migration: BST1 functions as a receptor for growth factor-primed neutrophil transendothelial migration
Pre-B cell growth: BST1 was originally identified as a stromal cell factor supporting pre-B lymphocyte growth
Monocyte/macrophage activation: BST1 engagement promotes inflammatory cytokine production
Brain Functions
Expressed in [microglia](/cell-types/microglia), [astrocytes](/cell-types/astrocytes), and neurons at low-moderate levels
Microglial BST1 regulates calcium-dependent phagocytosis and inflammatory responses
Neuronal BST1 contributes to calcium homeostasis and synaptic function
NAD+ metabolism through BST1 intersects with [SIRT1](/genes/sirt1)/[SIRT2](/genes/sirt2) sirtuin-dependent neuroprotection pathways
Role in Disease
Parkinson's Disease
BST1 is a genome-wide significant PD risk locus identified in multiple GWAS:
Lead SNP: rs4698412 (4p15.32, p < 5×10−8 in combined Asian and European populations)
Risk mechanism: Risk alleles are associated with altered BST1 expression, potentially affecting microglial calcium signaling and NAD+ metabolism
Microglial inflammation: Dysregulated BST1 activity may enhance microglial inflammatory responses through cADPR-mediated calcium mobilization
NAD+ depletion: Excessive BST1 NADase activity could deplete neuronal NAD+ pools, impairing sirtuin-dependent mitochondrial quality control and [PINK1](/genes/pink1)/[Parkin](/genes/prkn) pathway function
Dopaminergic vulnerability: Calcium dysregulation through BST1/TRPM2 signaling may increase susceptibility of [substantia nigra dopaminergic neurons](/cell-types/substantia-nigra-dopaminergic-neurons), which already have elevated calcium demands
[Nalls MA et al., Identification of novel risk loci, causal insights, and heritable risk for Parkinson disease: a meta-analysis of genome-wide association studies (2019) (2019)](https://doi.org/10.1016/S1474-4422(19)
[Satake W et al., Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease (2009) (2009)](https://doi.org/10.1038/ng.485)
[Hirata Y et al., ADP ribosyl cyclase activity of a novel bone marrow stromal cell surface molecule, BST-1 (1994) (1994)](https://doi.org/10.1016/0014-5793(94)
[Saad M et al., Genome-wide association study confirms BST1 and suggests a locus on 12q24 as the risk loci for Parkinson's disease in the European population (2011) (2011)](https://doi.org/10.1093/hmg/ddr027)
[Malavasi F et al., Evolution and function of the ADP ribosyl cyclase/CD38 gene family in physiology and pathology (2008) (2008)](https://doi.org/10.1152/physrev.00035.2007)