Deubiquitinase that mediates 'Lys-63'-linked deubiquitination of tight junction proteins, such as MARVELD2 and LSR, and which is involved in the survival of auditory hair cells and hearing (PubMed:32124521, PubMed:39587316). Specifically cleaves 'Lys-63'- linked polyubiquitin chains composed of at least 3 ubiquitin molecules, while it is not able to deubiquitinate substrates with shorter ubiquitin chains: recognizes ubiquitin chain in position S2 and catalyzes en bloc cleavage of polyubiquitin chains from substrate proteins (PubMed:39587316). Probably acts by modulating the barrier properties and mechanical stability of tight junctions via deubiquitination of MARVELD2 and LSR (PubMed:32124521, PubMed:39587316). {ECO:0000269|PubMed:32124521, ECO:0000269|PubMed:39587316}. This is the function of USP53 (ubiquitin specific peptidase 53, ENSG00000145390).