PTPRG (protein tyrosine phosphatase receptor type G) is a transmembrane receptor phosphatase that regulates cellular signaling through its tyrosine phosphatase activity. The protein contains a carbonic anhydrase-like domain and fibronectin type III domain in its N-terminal region, which may function as a bicarbonate sensor and cell adhesion domain, respectively 1. PTPRG acts as a tumor suppressor by dephosphorylating downstream targets of RAS signaling, particularly ERK, and its expression can be upregulated by RAS activation under DNA hypomethylating conditions 2. The gene is frequently silenced by DNA methylation in various cancers, including gastric cancer and childhood acute lymphoblastic leukemia, where methylation status correlates inversely with gene expression 32. Treatment with DNA methylation inhibitors like 5-Aza-2'-deoxycytidine can restore PTPRG expression 3. PTPRG variants show genome-wide significant association with Alzheimer's disease risk in family-based studies 4, though no significant association was found with Fuchs' corneal dystrophy 5. The gene's antisense RNA, PTPRG-AS1, functions as a competing endogenous RNA that promotes gastric cancer progression through the KITLG/KIT pathway 6.