Tmem59, also known as DCF1 (dendritic cell-derived factor 1), is a type I transmembrane protein. It is involved in multiple biological processes. It has been linked to autophagy, as it contains a peptide in its intracellular domain that can interact with ATG16L1, promoting local activation of LC3 and potentially targeting specific membranous compartments for autophagic degradation [5]. It also potentiates Wnt signaling by promoting the formation of Wnt signalosomes [4].

In gene knockout studies, Tmem59-deficient mice have provided valuable insights. Microglial-specific Tmem59 knockout mice develop autism-like behaviors, with impaired synapse phagocytosis, enhanced excitatory synaptic transmission, and increased dendritic spine density, suggesting its role in synapse refinement during brain development [1]. TMEM59 ablation in mice leads to loss of olfactory sensory neurons, impairs olfactory functions, and disrupts the balance between epithelial maintenance and inflammation [2]. In the context of cerebral ischemic stroke, TMEM59 knockout in mice exacerbates infarction volume, neurological deficits, and microglial activation and pyroptosis, indicating its protective role against ischemic stroke [3].

In summary, Tmem59 plays crucial roles in various biological processes, especially in the nervous system. Studies using KO mouse models have revealed its importance in synapse refinement, olfactory function, and protection against cerebral ischemic stroke, providing a better understanding of related disease mechanisms and potential therapeutic targets.