GRAMD1C encodes Aster-C, a non-vesicular cholesterol transporter that mediates cholesterol movement from the plasma membrane (PM) to the endoplasmic reticulum (ER). The protein localizes to ER-PM contact sites (EPCS) via its GRAM domain and uses its VASt/ASTER sterol-binding domain to facilitate cholesterol transfer 1. Despite its proposed role in cholesterol homeostasis, GRAMD1C appears to play a minor role in whole-body cholesterol balance, as Gramd1c-knockout mice showed no significant alterations in fecal, liver, or plasma cholesterol under low or high dietary conditions, though modest effects on bile acid and cortisol levels were observed under lipid-poor conditions 1. In the context of disease, GRAMD1C has emerged as a potential prognostic biomarker and therapeutic target across multiple malignancies. Genetically predicted reduced GRAMD1C levels associated with decreased ovarian cancer risk in Mendelian randomization analysis 2. GRAMD1C showed prognostic significance for hepatocellular carcinoma and was identified as part of a five-gene cholesterogenic signature for predicting young breast cancer prognosis, where lower expression correlated with better outcomes 3, 4. Additionally, GRAMD1C was identified in a four-gene diagnostic signature for distinguishing pediatric sepsis patients from healthy controls 5. These findings suggest GRAMD1C's expression patterns may serve as biomarkers across diverse disease contexts, though its specific mechanistic contributions remain incompletely understood.