VSX1 (visual system homeobox 1) is a paired-like homeodomain transcription factor that binds to the 37-bp core of the locus control region of the red/green visual pigment gene cluster and regulates cone opsin genes during retinal development 1. The gene is expressed in embryonic craniofacial tissues and adult ocular tissues, particularly in the retinal inner nuclear layer 23. VSX1 plays a critical role in ocular development through its DNA-binding transcription factor activity 2. Regarding disease relevance, VSX1 variants show population-specific associations with keratoconus. In Malaysian patients, the p.A182A and p.P237P variants were significantly associated with keratoconus susceptibility, while p.R217H appeared protective 4. A novel variant p.Leu268His identified in Indian families co-segregated with keratoconus and was predicted deleterious 5. However, multiple studies in other populations (Korean and white American cohorts) failed to confirm VSX1 mutations as pathogenic in keratoconus, suggesting population-specific genetic heterogeneity 67. Clinically, VSX1 is implicated in craniofacial anomalies and anterior segment dysgenesis syndrome. Additionally, recent evidence indicates VSX1 functions as an oncogenic transcription factor in clear cell renal cell carcinoma, where high expression promotes cell proliferation and invasion through FKBP10 transcriptional regulation 8.