HILPDA — Hypoxia Inducible Lipid Droplet Associated Protein
Overview
HILPDA (Hypoxia Inducible Lipid Droplet Associated) is a gene located on chromosome 12q13.13 that encodes a small secreted protein involved in lipid metabolism and cellular stress responses. Originally identified as a hypoxia-inducible gene, HILPDA plays important roles in regulating lipid droplet formation, triglyceride storage, and cellular adaptation to metabolic stress. Recent research suggests HILPDA may have important implications for neurodegenerative diseases through its effects on lipid homeostasis and neuroinflammation.
The protein encoded by HILPDA is available at [HILPDA Protein](/proteins/hilpda-protein).
Function
Normal Physiological Functions
HILPDA is a small 125-amino acid protein that localizes to lipid droplets in response to hypoxic conditions. Its primary functions include:
Lipid droplet regulation: Promotes lipid droplet formation and triglyceride accumulation under hypoxic conditions
Hypoxia response: Activated by HIF-1α (Hypoxia-Inducible Factor 1-alpha) during oxygen deprivation
Metabolic adaptation: Helps cells survive nutrient and oxygen deprivation by regulating lipid metabolism
Endocrine functions: Secreted HILPDA can act on distant tissues to regulate systemic metabolism
Brain Expression
HILPDA is expressed in multiple brain regions:
Cerebral cortex ([neurons](/entities/neurons) and glial cells)
Hippocampus (pyramidal neurons)
Hypothalamus (regulating metabolic homeostasis)
White matter (oligodendrocytes)
Expression is upregulated in conditions of hypoxia and metabolic stress.
Role in Neurodegeneration
Lipid Metabolism Dysregulation
Emerging evidence links HILPDA to neurodegenerative diseases through lipid metabolism pathways:
Alzheimer's Disease: Altered lipid metabolism is a hallmark of AD. HILPDA expression is elevated in AD brains, potentially reflecting cellular stress responses to amyloid and [tau](/proteins/tau) pathology
Parkinson's Disease: Lipid droplet accumulation in dopaminergic neurons is observed in PD models. HILPDA may contribute to this phenotype
Lipotoxicity: Dysregulated HILPDA may lead to lipid droplet accumulation in neurons, causing lipotoxicity and neuronal dysfunction
Neuroinflammation
HILPDA is involved in regulating neuroinflammatory responses:
Microglial activation states are influenced by lipid metabolism
Metabolic inflammation (metaflammation) may be amplified by HILPDA dysregulation
Potential interaction with [complement system](/entities/complement-system) activation
Mitochondrial Function
HILPDA affects mitochondrial function indirectly through its effects on lipid metabolism:
Lipid droplet-mitochondria contact sites regulate mitochondrial function