In summary, through proteomic analyses of urinary exosomes from humanized SCD mice, and subsequent Western blot confirmation using urine and urinary exosomes of SCD subjects, we have observed that both male and female SCD subjects exhibited an increased or trending increase in the excretion of heparanase, cathepsin C, α2-macroglobulin, and SERCA3 proteins. Here, HPSE is linked to Schnyder corneal dystrophy.