GRAM domain-containing protein 1C (GRAMD1C)

GRAM domain-containing protein 1C (GRAMD1C, also known as protein Aster-C) is an endoplasmic reticulum-anchored sterol transporter protein predominantly expressed in the liver and testes[1][6]. It contains both a GRAM domain—which targets it to membrane contact sites—and a VASt domain that binds cholesterol[1][4][5]. GRAMD1C mediates non-vesicular cholesterol transfer from the plasma membrane to the ER, facilitating overall cellular cholesterol redistribution and feedback regulation via SREBP signaling[2]. It also regulates autophagy negatively by suppressing autophagosome initiation and influences mitochondrial cholesterol content and bioenergetics[4][5]. Differential expression and activity of GRAMD1C have been implicated in liver disease and various cancers, making it a molecular target for modulation of cholesterol homeostasis, autophagy, and cell survival[2][4][5]. Selective chemical inhibitors of GRAMD1C have recently been developed as molecular probes, but no approved drugs currently target this protein[3].

Other names

Protein Aster-CAster-CUNQ2543/PRO6095DKFZp434C0328GRAM domain-containing protein 1C

AI-1l: Selective inhibition of GRAMD1C’s cholesterol-binding and transport activity AI-3d: Pan-inhibition of Aster family’s cholesterol transfer function in vitro and in cells