GRAMD1A is a cholesterol transporter that mediates non-vesicular cholesterol transport from the plasma membrane (PM) to the endoplasmic reticulum (ER), playing a critical role in cellular cholesterol homeostasis 1. The protein contains a GRAM domain that binds phosphatidylserine and mediates recruitment to ER-PM contact sites in response to PM cholesterol accumulation, while its StART-like domain binds and facilitates cholesterol extraction 2. Beyond cholesterol transport, GRAMD1A regulates autophagosome biogenesis through its cholesterol-transfer activity, accumulating at autophagosome initiation sites and affecting cholesterol distribution during starvation 3. Clinically, GRAMD1A has emerged as a significant biomarker in multiple cancers. In colorectal cancer, KRAS mutation increases GRAMD1A expression via histone H3 lysine 9 lactylation, promoting CRC growth and metastasis through enhanced cholesterol metabolism 4. In kidney renal clear cell carcinoma, GRAMD1A shows diagnostic value (AUC: 0.942) and serves as an independent prognostic factor associated with shorter survival and immune infiltration patterns 5. Similarly, in hepatocellular carcinoma, GRAMD1A is upregulated through the circCAMSAP1-miR-1294 axis and promotes tumor progression 6. Additionally, GRAMD1A autoantibodies show potential as diagnostic markers for seronegative Sjögren's disease 7.