Tmem184b, a transmembrane protein, has diverse essential functions. It is involved in multiple biological processes, such as axon degeneration, synaptic maintenance, and endolysosomal acidification [3,4]. It may also play a role in regulating the expression of genes related to neural development and synaptic function, and is associated with the Wnt signaling pathway [2]. Genetic models, like KO mouse models, have been crucial for studying its functions.

In KO mouse models, loss of Tmem184b leads to phenotypes including delayed axon degeneration after nerve injury, abnormal neuromuscular junction architecture, and sensory-motor function deficits, indicating its importance in peripheral nerve terminal structure and function [3]. In the retina, Tmem184b deletion causes retina degeneration, with reduced electroretinogram amplitudes, retinal thinning, and cell death [5]. In humans, de novo heterozygous variants in TMEM184B are associated with neurodevelopmental deficits, and zebrafish with suppressed Tmem184B ortholog show microcephaly and reduced anterior commissural neurons, suggesting its role in neural development [1].

In conclusion, Tmem184b is vital for the normal development and function of the nervous system, as demonstrated by model-based research. Its disruption can lead to neurodevelopmental syndromes, retina degeneration, and abnormal sensory-motor function, highlighting its significance in understanding these disease areas.

References:

1. Chapman, Kimberly A, Ullah, Farid, Yahiku, Zachary A, Davis, Erica E, Bhattacharya, Martha Rc. 2024. Pathogenic variants in TMEM184B cause a neurodevelopmental syndrome via alteration of metabolic signaling. In medRxiv : the preprint server for health sciences, , . doi:10.1101/2024.06.27.24309417. https://pubmed.ncbi.nlm.nih.gov/39006436/

2. Wright, Elizabeth B, Larsen, Erik G, Coloma-Roessle, Cecilia M, Hart, Hannah R, Bhattacharya, Martha R C. 2023. Transmembrane protein 184B (TMEM184B) promotes expression of synaptic gene networks in the mouse hippocampus. In BMC genomics, 24, 559. doi:10.1186/s12864-023-09676-9. https://pubmed.ncbi.nlm.nih.gov/37730546/

3. Bhattacharya, Martha R C, Geisler, Stefanie, Pittman, Sara K, Milbrandt, Jeffrey, DiAntonio, Aaron. . TMEM184b Promotes Axon Degeneration and Neuromuscular Junction Maintenance. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 36, 4681-9. doi:10.1523/JNEUROSCI.2893-15.2016. https://pubmed.ncbi.nlm.nih.gov/27122027/

4. Wright, Elizabeth B, Larsen, Erik G, Padilla-Rodriguez, Marco, Langlais, Paul R, Bhattacharya, Martha R C. 2025. Neuronal endolysosomal acidification relies on interactions between transmembrane protein 184B (TMEM184B) and the vesicular proton pump. In bioRxiv : the preprint server for biology, , . doi:10.1101/2025.02.01.635992. https://pubmed.ncbi.nlm.nih.gov/39975166/

5. Liu, Guo, Liu, Tiannan, Tan, Junkai, Yang, Yeming, Zhu, Xianjun. 2024. Deletion of Transmembrane protein 184b leads to retina degeneration in mice. In Cell proliferation, 58, e13751. doi:10.1111/cpr.13751. https://pubmed.ncbi.nlm.nih.gov/39375958/