The ancient metazoan cytoplasmic intermediate filament protein, Cilin, shapes cilia arrangement and tissue architecture

The emergence of animal multicellularity demanded novel cytoskeletal systems to support cellular architecture and tissue integrity. Cytoplasmic intermediate filaments (cIFs) are essential components of this scaffold, yet their evolutionary origins remain obscure. Here, we identify and characterize a lamin-derived, bona fide cIF protein in a ctenophore--a sister lineage to all other extant animals. We name this protein Cilin. Unlike nuclear lamins, Cilin lacks a nuclear localization signal and instead localizes predominantly to motile ciliary structures, including comb plates, the aboral organ, and sperm flagella, indicating a central role in ciliary architecture and function. Remarkably, Cilin is also present in non-ciliated cells, suggesting early functional diversification of cIFs in animal evolution. Phylogenetic and structural analyses position Cilin within an ancestral class of intermediate filament proteins, homologous to cnidarian and bilaterian nematocilins and lamin-tail-domain-containing (LMNTD) proteins. In humans, LMNTD proteins are enriched in ciliated epithelia and spermatids, pointing to a deeply conserved role in cilia-associated functions. These findings establish cilins as the earliest lamin-derived cytoplasmic intermediate filament proteins in metazoans, likely contributing to both ciliary function and the emergence of multicellular tissue organization.