SMPD3 and neoplasm: RNAi-mediated gene knockdowns of Rab27a or Rab27b have been reported to inhibit sEV secretion in various tumor cells, including BCa cells,225 HNSCCs,224,226 and cervical cancer cells.39 Similarly, Poggio et al. used CRISPR-Cas9 to knock out nSMase2 or Rab27a, achieving inhibition of sEV secretion in prostate cancer cells.227 However, deleting nSMase2 only partially eliminated TDSEVs, indicating the need for further investigation into more effective strategies or targets.