Specifically deubiquitinates 'Lys-14' (H2AK13Ub) and 'Lys- 16'(H2AK15Ub) of histone H2A regulating the DNA damage response at double-strand breaks (DSBs) (PubMed:27083998, PubMed:33022275). USP51 is recruited to chromatin after DNA damage and regulates the dynamic assembly/disassembly of TP53BP1 and BRCA1. Functions in DNA double- strand break repair also by mediating the deubiquitination and subsequent stabilization of DGCR8, leading to the recruitment of DGCR8 binding partners to double strand breaks such as RNF168 or MDC1 (PubMed:34188037). In addition, promotes the deubiquitination and stabilization of the transcriptional repressor ZEB1 (PubMed:29119051). {ECO:0000269|PubMed:27083998, ECO:0000269|PubMed:29119051, ECO:0000269|PubMed:33022275, ECO:0000269|PubMed:34188037}. This is the function of ENSG00000247746 (USP51, ubiquitin specific peptidase 51).