TMEM97

Sigma-2 receptor implicated in the regulation of multiple cellular processes, including cholesterol biosynthesis and trafficking, membrane trafficking, autophagy, lipid membrane-associated protein trafficking, and stabilization of receptors at the cell surface, thereby contributing to the maintenance of cellular homeostasis. Forms a ternary complex with PGRMC1 and LDLR at the plasma membrane, promoting LDLR-mediated internalization of LDL cholesterol. Reduces the availability of the lysosomal sterol transporter NPC1, likely through direct interaction, thereby regulating lipid transport, including cholesterol and LBPA, outside of late endosome/lysosome. Binds the regio- and stereoselective oxysterol 20(S)-hydroxycholesterol (20(S)-OHC). Ligand binding enhances association with NPC1 and modulates TMEM97-containing protein complexes involving PGRMC1 and TSPO, consistent with a role in cholesterol homeostasis. Also able to bind cholesterol (By similarity). Interacts with the salivary peptide histatin 1 (Hst 1/HTN1) at the ER membrane, which is critical for increasing mitochondria-ER contacts and stimulating Hst 1 wound healing properties. May alter the activity of some cytochrome P450 proteins. Although sharing homology with sterol isomerases through the EXPERA domain, lacks sterol isomerase activity; instead, may function as a sterol or oxysterol sensor. Acts as an ER quality control factor by promoting proteolytic degradation of nonproductive and extramitochondrial precursor proteins in the ER membrane, thereby removing them from the ER surface (By similarity)..

Function from UniProtKB (Q5BJF2), read 2026-09-23. CC BY 4.0.