Primary cilia: turning points in establishing their ubiquity, sensory role and the pathological consequences of dysfunction.

For over 20 years it has finally become accepted that primary cilia are without doubt important cellular organelles, involved in signalling both intrinsically and extrinsically. The consequences of their agenesis, incorrect assembly and dysfunction only began to be fully appreciated after 2000, although this had been demonstrable over the previous two decades. Before 1980, biologists at large thought the organelle rudimentary or vestigial; how a well-developed cilium could be so slated beggars belief. Many pathological conditions have implicated the primary cilium as either a major or contributing factor, ranging from kidney malfunction (e.g. polycystic kidney disease) to mental aberrations. However, the questions of how the recognition of their prevalence, their sensory function, and their pathological involvement finally emerged as substantiated and verifiable facts needs to be addressed because what happened before the 1980s, and then notably between 1980 and 2000, can help guide research towards answering further questions on these issues. Here the intention is to focus on the salient findings (the turning points) that brought about changes in our knowledge of primary cilia. The literature on them is growing fast, with the total moving towards 20,000 reports, of which > 60% have been published in the last decade. PubMed indicates that nearly 1000 papers were published in 2020 alone. We also have to appreciate that the primary cilium can assume many different forms, each of which means that there must be many genes responsible for their development and final structure. This also suggests that there are many more functions than are currently known in both their sensory reception and signalling properties, probably for many highly specialised purposes. Malfunctioning in any of these roles will undoubtedly uncover further pathological conditions.