Bbs4 is one of the genes associated with Bardet-Biedl syndrome (BBS), a rare autosomal recessive ciliopathy. The BBS genes encode proteins localizing to cilia and basal bodies, involved in cilia biogenesis and function [1]. Bbs4 is crucial for normal cilia-related functions and may also have extra-ciliary roles, and its study using genetic models can help understand its functions in vivo.

In Bbs4 -/- mice, olfactory sensory neuron (OSN) cilia are shorter and fewer, with asynchronous intraflagellar transport (IFT) particle movements, indicating miscoordination in IFT complex trafficking. Also, basal body numbers are reduced. Adenoviral expression of BBS4 can restore OSN cilia lengths and odor detection but not ciliary and basal body numbers [2]. In adipocytes, silencing Bbs4 leads to accelerated cell division, aberrant differentiation, and greater triglyceride accumulation. Bbs4 is also involved in adipocyte endoplasmic reticulum (ER) stress response, with its depletion resulting in swollen ER and impaired nuclear translocation of XBP-1 and ATF6α [4,5]. In neuronal cells, BBS4 silencing reduces sensitivity to ER stress during differentiation, as sXBP-1 and activated ATF6α p50 fail to translocate to the nucleus [3].

In conclusion, Bbs4 is essential for cilia-related functions in olfactory neurons and plays significant roles in adipocyte and neuronal development and stress responses. Studies using Bbs4 knockout mouse models have provided insights into the mechanisms underlying BBS-associated phenotypes such as obesity, olfactory dysfunction, and potential neural development abnormalities.