Otoferlin is alternatively spliced in cochlea and brain. Otoferlin is expressed in multiple tissues and organs (34). C2 domains A–F and the C-terminal transmembrane (TM) domains of cochlear and brain otoferlin are illustrated. Of the six C2 domains, four (C2C–C2F) are predicted to bind calcium. In the cochlea, an otoferlin transmembrane domain splice variant arises from exon 48, whereas in brain, it originates from exon 47. The amino acid sequence coded by exon 48 is 72% identical to that of exon 47. Neuronal synaptic vesicles do not contain otoferlin (32), whereas synaptosomal fractions from chick cochleas, which include hair cell synaptic vesicles, do contain otoferlin (33), possibly in parallel with the different transmembrane domains yielding different membrane inserts and localizations of the respective otoferlin molecules. In contrast to the differences in transmembrane sequence, the C2 domains of otoferlin for brain and cochlea are 100% identical.