Gramd1c, also known as Aster-C, encodes an endoplasmic reticulum (ER) resident protein involved in non-vesicular cholesterol transport [1,6]. It is crucial for maintaining cellular cholesterol distribution, especially at the ER-Golgi contact sites, by transporting excess cholesterol from the Golgi to the ER [1]. Additionally, GRAMD1C functions as a negative regulator of starvation-induced autophagy and may facilitate cholesterol transfer at ER-mitochondria contact sites [2,3]. It is also associated with pathways like mTOR signaling, RNA degradation, WNT signaling, toll pathway, and AKT pathway in kidney renal clear cell carcinoma (KIRC) [4].

In mice globally lacking Aster-C (Gramd1c -/ -), there were no significant alterations in fecal, liver, or plasma cholesterol under low or high dietary cholesterol conditions. However, under low dietary cholesterol, there were modest changes in select bile acid species and elevated cortisol levels [6]. In PC12 cells, knocking down GRAMD1C expression reduced 6-OHDA-induced apoptosis, suggesting its role in the apoptotic pathway related to Parkinson's disease [5]. In KIRC, reduced GRAMD1C expression correlated with poor prognosis and was significantly associated with tumor-infiltrating immune cells, especially regulatory T cells (Tregs) [4].

In summary, Gramd1c plays important roles in cellular cholesterol distribution, autophagy regulation, and is associated with diseases like Parkinson's disease and KIRC. Gene-knockout mouse models have provided insights into its role in whole-body cholesterol balance and in disease-related cellular processes such as apoptosis and immune infiltration in specific disease contexts [4,5,6].