Enrichment of APOBEC hypermutation signatures has been observed in cohorts of patients with SCLC tumors undergoing phenotypic transformation, highlighting its role in facilitating tumor plasticity under therapeutic pressure.19 Recent findings have elucidated the mechanisms underlying APOBEC-driven mutagenesis, with the loss of SYNCRIP, an RNA-binding protein that inhibits APOBEC3B activity, identified as a key contributor.126 The loss of SYNCRIP unleashes unchecked APOBEC3B activity, leading to extensive mutational processes that target critical regulatory genes. Here, SYNCRIP is linked to neoplasm.