VSX1 encodes a paired-like homeodomain transcription factor that binds the 37-bp core of the locus control region of the red/green visual pigment gene cluster and regulates cone opsin genes during ocular development [10903837]. The protein contains a conserved CVC domain and functions as a DNA-binding transcription factor expressed in embryonic craniofacial and adult ocular tissues, particularly the retina's inner nuclear layer. VSX1 variants have been associated with keratoconus in some populations. In Malaysian patients, the p.A182A and p.P237P variants showed significant association with keratoconus risk (odds ratio 3.14–4.05) and appeared to be co-inherited 1, while the p.R217H variant was protective. In Indian families, the novel p.Leu268His substitution co-segregated with keratoconus and demonstrated in silico evidence of deleterious effects 2. However, studies in Korean and white populations failed to confirm VSX1 variants as major contributors to keratoconus pathogenesis 34. Mutations affecting the homeodomain (R166W) or CVC domain (G160D, P247R) have been identified in posterior polymorphous dystrophy and severe keratoconus, with some mutations associated with abnormal inner retinal function on electroretinography 5. Recent evidence suggests VSX1 plays an oncogenic role in clear cell renal cell carcinoma, with high expression associated with unfavorable prognosis and enhanced cell proliferation and invasion via transcriptional regulation of FKBP10 and related targets 6.