PKHD1L1 encodes a large type I transmembrane protein that serves as a critical component of the stereocilia coat in cochlear hair cells, playing an essential role in auditory function 1. The protein is required for maintaining stereocilia bundle cohesion and structural integrity throughout life, with PKHD1L1-deficient mice showing progressive deterioration of hair bundles starting at 6 weeks of age 2. Mechanistically, PKHD1L1 establishes robust sensory hair bundles during development that are necessary for maintaining bundle function in response to acoustic trauma and aging 2. Loss-of-function mutations destabilize protein structure and folding, compromising stereocilia coat formation 1. PKHD1L1 deficiency causes autosomal recessive nonsyndromic sensorineural hearing loss (DFNB124) in humans, with patients exhibiting mild-moderate to severe hearing impairment 1. Animal models demonstrate progressive high-frequency hearing loss that extends to lower frequencies with age, and increased susceptibility to permanent noise-induced hearing damage 2. The gene's function in hearing is evolutionarily conserved, as zebrafish pkhd1l1 mutations also cause hearing deficits 3. Beyond auditory function, PKHD1L1 shows associations with immune cell infiltration and may have roles in cancer prognosis, though these functions require further investigation 4.