Both male and female SCD subjects with albuminuria exhibit significantly increased or tend to excrete higher levels of heparanase, cathepsin C, and α2-macroglobulin in their urine compared to those without albuminuria, but only female subjects demonstrated superior correlations between the excretion of these proteins in urinary exosomes and urine, in contrast to male subjects. To expedite detection, we explored whether heparanase, cathepsin C, α2-macroglobulin, and SERCA3 could be directly identified in participants’ urine using Western blot analysis. Here, HPSE is linked to Schnyder corneal dystrophy.