X-linked deafness (DFNX) is estimated to account for up to 2% of cases of hereditary hearing loss and occurs in both syndromic and non-syndromic forms. POU3F4 is the gene most commonly associated with X-linked deafness (DFNX2, DFN3) and accounts for about 50% of the cases of X-linked non-syndromic hearing loss. This gene codes for a transcription factor of the POU family that plays a major role in the development of the middle and inner ear. The clinical features of POU3F4-related hearing loss include a pathognomonic malformation of the inner ear defined as incomplete partition of the cochlea type 3 (IP-III). Often, a perilymphatic gusher is observed upon stapedectomy during surgery, possibly as a consequence of an incomplete separation of the cochlea from the internal auditory canal. Here we present an overview of the pathogenic gene variants of POU3F4 reported in the literature and discuss the associated clinical features, including hearing loss combined with additional phenotypes such as cognitive and motor developmental delays. Research on the transcriptional targets of POU3F4 in the ear and brain is in its early stages and is expected to greatly advance our understanding of the pathophysiology of POU3F4-linked hearing loss.