TMEM98 is a transmembrane protein with dual roles in ocular development and cellular regulation. Primary function: TMEM98 negatively regulates MYRF, an ER-tethered transcription factor involved in eye size specification 1. It inhibits MYRF self-cleavage and nuclear translocation of the N-terminal fragment, thereby suppressing MYRF-dependent transcription 1. In the retinal pigment epithelium, TMEM98 loss leads to enlarged, fragile eyes with thin retinas and sclera, demonstrating its critical role in controlling ocular dimensions 1. Disease relevance: Mutations in TMEM98 cause nanophthalmos 4, characterized by abnormally small eyes, high hyperopia, and angle-closure glaucoma predisposition 234. The A193P and I135T missense mutations produce recessive retinal defects featuring photoreceptor layer disruption, retinal folds, and outer segment accumulation 2. Patients with TMEM98 variants show earlier glaucoma onset compared to other nanophthalmos genes 4. Clinical significance: Beyond ocular function, TMEM98 demonstrates multifaceted involvement in cancer biology. Elevated TMEM98 expression in hepatocellular carcinoma (67.8% of specimens) correlates with early recurrence, poor survival, and chemoresistance through AKT pathway activation 56. Conversely, TMEM98 acts as a tumor suppressor in ovarian cancer, with low expression promoting proliferation and inhibiting apoptosis 7. TMEM98 knockdown inhibits lung cancer cell invasion and migration 8, indicating context-dependent oncological roles.