BACKGROUND: The mammalian otoconial membrane is a dense extracellular matrix 
containing bio-mineralized otoconia. This structure provides the mechanical 
stimulus necessary for hair cells of the vestibular maculae to respond to linear 
accelerations and gravity. In teleosts, Otolin is required for the proper 
anchoring of otolith crystals to the sensory maculae. Otoconia detachment and 
subsequent entrapment in the semicircular canals can result in benign paroxysmal 
positional vertigo (BPPV), a common form of vertigo for which the molecular 
basis is unknown. Several cDNAs encoding protein components of the mammalian 
otoconia and otoconial membrane have recently been identified, and mutations in 
these genes result in abnormal otoconia formation and balance deficits.
PRINCIPAL FINDINGS: Here we describe the cloning and characterization of 
mammalian Otolin, a protein constituent of otoconia and the otoconial membrane. 
Otolin is a secreted glycoprotein of ∼70 kDa, with a C-terminal globular domain 
that is homologous to the immune complement C1q, and contains extensive 
posttranslational modifications including hydroxylated prolines and glycosylated 
lysines. Like all C1q/TNF family members, Otolin multimerizes into higher order 
oligomeric complexes. The expression of otolin mRNA is restricted to the inner 
ear, and immunohistochemical analysis identified Otolin protein in support cells 
of the vestibular maculae and semi-circular canal cristae. Additionally, Otolin 
forms protein complexes with Cerebellin-1 and Otoconin-90, two protein 
constituents of the otoconia, when expressed in vitro. Otolin was also found in 
subsets of support cells and non-sensory cells of the cochlea, suggesting that 
Otolin is also a component of the tectorial membrane.
CONCLUSION: Given the importance of Otolin in lower organisms, the molecular 
cloning and biochemical characterization of the mammalian Otolin protein may 
lead to a better understanding of otoconial development and vestibular 
dysfunction.