PRSS56 encodes a trypsin-like serine protease required for normal eye development 1. During ocular morphogenesis, PRSS56 is expressed by Müller glia in the retina 2 and functions as a serine-type endopeptidase involved in proteolytic processes critical for establishing proper eye size and posterior segment development 3. The gene regulates scleral remodeling and myosin-4 abundance, directly controlling axial length elongation 1. PRSS56 mutations cause nanophthalmos and posterior microphthalmia, characterized by shortened axial length and extreme hyperopia 34. Notably, noncoding PRSS56 promoter variants increase expression through enhanced EGR1 transcription factor binding, causing high myopia with excessive axial elongation 1. Among nanophthalmos patients, PRSS56 variants (47.6% of cases) associate with severe uveal effusion and angle-closure glaucoma, the latter occurring in 79.1% of affected patients 45. PRSS56 emerges as a therapeutic target for juvenile high myopia, as short-wave light exposure reduces expression and attenuates axial elongation 1. The gene's dysregulation demonstrates bidirectional effects on eye size—loss-of-function causes microphthalmia while increased expression drives myopic elongation—highlighting PRSS56's central role in eye size determination.