Steroidogenic acute regulatory protein-related lipid transfer domain-containing protein 4 (STARD4) (STARD4)

Steroidogenic acute regulatory protein-related lipid transfer domain-containing protein 4 (STARD4) is a soluble lipid transfer protein that plays a critical role in maintaining cellular cholesterol homeostasis [UniProt: Q96DR4]. It belongs to the StarD4 subfamily of START domain proteins and specifically facilitates the non-vesicular transport of cholesterol between various intracellular membranes, most notably from the plasma membrane to the endoplasmic reticulum (ER) [PubMed: 22354080]. In the ER, this cholesterol is either sensed by the SREBP pathway to regulate gene expression or esterified by ACAT for storage [PubMed: 12531898]. STARD4 expression is transcriptionally regulated by sterol regulatory element-binding protein 2 (SREBP-2), making it a key component of the cell's feedback response to low cholesterol levels [PubMed: 12531898]. Dysregulation of STARD4 has been implicated in metabolic disorders such as atherosclerosis and non-alcoholic fatty liver disease due to its impact on lipid accumulation and ER stress [PubMed: 26354434]. While no clinical drugs currently target STARD4 directly, it represents a potential therapeutic target for modulating intracellular cholesterol distribution and treating lipid-related pathologies [PubMed: 28655635].

Other names

StARD4START domain-containing protein 4

STARD4 facilitates the non-vesicular transport of cholesterol between the plasma membrane and the endoplasmic reticulum or mitochondria, thereby regulating intracellular sterol distribution and sensing [PubMed: 22354080].