33−36 A better elucidation of the implication of σ2Rsin tumor cell death was reported in 2019 by Zeng and co-workers, whichconducted CRISPR/Cas9 studies to assess the cytotoxic properties ofσ2R ligands in TMEM97 knockout (KO), PGRMC1 KO, orTMEM97/PGRMC1 double KO cell lines.37 Resultsshowed that induction of cell death by σ2R ligandswas not hampered, suggesting that the cytotoxic effects are not directlymediated by TMEM97 or PGRMC1, thus questioning the exact cytotoxicmechanism exerted by σ2R ligands. Here, TMEM97 is linked to neoplasm.