Protocadherin-15 (Pcdh15) belongs to the epsilon subfamily of nonclustered protocadherins. It is a component of the tip-links, the extracellular filaments that connect the tips of stereocilia and gate hair cell mechano-electrical transduction channels in the inner ear []. Pcdh15 interacts with transmembrane channel-like proteins TMC1 and TMC2, which have been implicated in mechanotransduction in mammalian hair cells []. Mutations in genes coding for Pcdh15 cause deafness in both mice and humans [, ]. Pcdh15 plays an important role in hair-bundle morphogenesis [].The cadherin family consists of a large group of cell adhesion proteins. It can be classified into three subfamilies: classical cadherins, desmosomal cadherins and protocadherins (PCDHs). Based on the genomic structure, the PCDH family can be divided into two groups, clustered PCDHs and non-clustered PCDHs. Non-clustered PCDHs can be further classified into three subgroups: delta1 (PCDH1, PCDH7, PCDH9, PCDH11 and PCDH20), delta2 (PCDH8, PCDH10, PCDH12, PCDH17, PCDH18 and PCDH19) and epsilon (PCDH15, PCDH16, PCDH21 and MUCDHL). Non-clustered PCDHs are expressed predominantly in the nervous system and have spatiotemporally diverse expression patterns [].
