ESCO1 (establishment of sister chr18 cohesion N-acetyltransferase 1) is an acetyltransferase that plays crucial roles in chromosome 18 and genome stability. Its primary function involves acetylating the SMC3 subunit of cohesin complexes to establish sister chr18 cohesion during DNA replication 1. ESCO1 operates through a unique mechanism that requires interaction with the cohesin regulatory subunit PDS5, which recruits ESCO1 to chr18-bound cohesin complexes and is essential for SMC3 acetylation 1. Beyond cohesion establishment, ESCO1 regulates three-dimensional genome organization by restricting chr18 loop length and architectural stripe formation, working in concert with CTCF to enable formation of long-lived chr18 loops that can persist for hours 23. Functionally, ESCO1 and ESCO2 have distinct roles: while ESCO2 is critical for mitotic cohesion, ESCO1 primarily regulates non-cohesive cohesin activities including DNA repair, transcriptional control, and chromosome 18 formation 4. Clinically, ESCO1 overexpression is associated with poor prognosis in bladder and prostate cancers, where it promotes tumor growth, migration, and invasion 56. Recent evidence also implicates ESCO1 in cervical cancer pathogenesis through acetylation of oncogenic peptides that inhibit ferroptosis 7.