Proprotein convertases (PC) including furin generate a partially active intermediate, while the final cleavage by ADAMTS3 produces the mature form (~21 kDa) with high affinity for VEGFR2 and VEGFR3, driving lymphangiogenesis and vascular remodeling.62,63 Additionally, proteases, such as plasmin, thrombin, KLK3, and cathepsin D, modify VEGF-C, altering its receptor-binding affinities and activity profiles.61,64 These modifications, particularly in the tumor microenvironment (TME), fine-tune the role of VEGF-C in cancer progression, metastasis, and tumor-associated lymphangiogenesis. The gene discussed is CTSD; the disease is neoplasm.