HPSE and neoplasm: For instance, the p53 protein, often aberrantly activated in cancer, is implicated in regulating sEV production and release by tumor cells.37 Heparanase, overexpressed in many tumor cell lines, also regulates sEV secretion.38 Moreover, Rap GTPase proteins, particularly Rab27a and Rab27b, which regulate secretory pathways, are strongly associated with sEV release.39,40 The knockdown of Rab proteins has been shown to reduce sEV secretion from tumor cells.40,41 Despite emerging insights into the regulation of sEV secretion by tumor cells, the precise mechanisms remain unclear.