Ubiquitin-Like with PHD and ring finger domains 2 (UHRF2), a member that belongs to the family of UHRF, contains five recognizable functional domains, namely the ubiquitin-like domain (UBL) domain, tandem-Tudor domain (TTD), plant homeodomain (PHD), SET and RING associated (SRA) domain, and really interesting new gene (RING) finger domain. Due to the complex structure, UHRF2 possesses multiple functions in diverse cellular processes. As a ubiquitin E3 ligase, UHRF2 could ubiquitinate PCNP, a nuclear protein that contains two remarkable PEST sequences which are rich in proline (P), glutamic acid (E), serine (S), and threonine (T). It has been also reported that UHRF2 could serve as a vital cell cycle regulator by interacting with multiple cyclins, CDKs, p53, pRB and PCNA. UHRF2 has been revealed to possess epigenetic regulation function and is capable of maintaining 5mC levels in certain genomic loci in brain and stabilizes TIP60 to regulate H3K9ac and H3K14ac through RING finger domain. Moreover, UHRF2 could promote DNA damage repair by reducing the level of p21 mediated by RING finger domain. Recently, emerging evidence indicated that UHRF2 was involved in the tumorigenesis and progression of several human cancers, such as esophageal squamous cell carcinoma, lung cancer and colorectal cancer. UHRF2 has 2 isoforms with the molecular mass of 56 and 90 kDa. (PMID: 34400880)