In the reverse causal study, melanoma was found to cause an increase in cathepsin E (OR = 1.051, 95% CI: 1.011–1.093, P < .05), while CSCC was found to cause an increase in cathepsin H (OR = 1.154, 95% CI: 1.045–1.273, P < .05) and cathepsin O (OR = 1.111, 95% CI: 1.006–1.226, P < .05). Here, CTSO is linked to skin squamous cell carcinoma.