Calml4, short for calmodulin-like protein 4, is a small EF-hand protein. It functions as a critical myosin light chain within the intermicrovillar adhesion complex (IMAC) in the intestine, playing a key role in assembling apical microvilli into an ordered brush border. It is also associated with the Usher complex, and disruption of this complex can lead to Usher syndrome type 1 (USH1) [1,2].

Genetic disruption of Calml4 within enterocytes results in brush border assembly defects similar to those seen with the loss of other IMAC components, highlighting its importance in this process [1]. In addition, Calml4 has been identified as a potential feature gene in osteoarthritis, with its mRNA expression level up-regulated in OA samples [3].

In a mouse model of polycystic ovary syndrome (PCOS), the cAMP signalling pathway, calcium signalling pathway and Calml4 may be related to improvements in hormone levels and ovarian follicle numbers after treatment with Leonurine hydrochloride [4].

In alcohol-withdrawn depressive rats, lavender essential oil inhalation regulated the aberrantly expressed Calml4 in the hippocampal region, alleviating depressive-like behavior [5].

In Cashmere bucks, inhibition of prolactin affected epididymal morphology, and Calml4 was enriched in pathways related to epididymal function [6].

Minocycline treatment in TBEV-infected cells decreased the level of Calml4, regulated the calcium signalling pathway-associated proteins, and inhibited the MAPK-ERK signalling pathway and inflammatory responses [7].

In summary, Calml4 is crucial for the proper assembly of the intermicrovillar adhesion complex in the intestine. Its role in various disease conditions such as osteoarthritis, PCOS, alcohol-induced depression, and tick-borne encephalitis virus infection has been identified through different research models. These findings contribute to understanding the biological functions of Calml4 and its potential implications in related diseases.