This study reveals Periaxin (Prx) gene variants that cause four amino acid substitutions in the cytoskeletal scaffold protein Periaxin (PRX) between C57BL/6J (B6) and 129S4 (129) mouse strains, modulating the severity of age-related cataracts in connexin 46 knockout (Cx46KO) mice. Here, PRX is linked to cataract.