ASPH (aspartate β-hydroxylase) is a membrane-bound, α-ketoglutarate-dependent dioxygenase that functions as a type II transmembrane protein 1. As a structural component of ER-plasma membrane junctions, ASPH regulates calcium ion homeostasis and store-operated calcium channel activity, with isoform 8 specifically regulating CRAC channels in T cells [UniProt annotation]. ASPH catalyzes post-translational hydroxylation of target proteins 2. Mechanistically, ASPH promotes tumor progression through multiple pathways: it enhances cell proliferation, migration, and invasion via Notch and SRC signaling activation 3; upregulates the SQSTM1/P62 and SLC7A11-GPX4 axis to promote autophagy while blocking ferroptosis 4; and facilitates epithelial-mesenchymal transition through GSK-3β/SHH/GLI2 signaling 2. ASPH expression is upregulated in hepatocellular carcinoma, pancreatic cancer, lung adenocarcinoma, breast cancer, and intrahepatic cholangiocarcinoma, consistently correlating with poor prognosis and therapeutic resistance 41562. High ASPH levels predict worse outcomes in sorafenib-treated HCC patients and promote tumor angiogenesis and immunosuppression 43. ASPH represents a promising therapeutic target through enzymatic inhibition, monoclonal antibodies, and immunotherapy approaches 3.