Lypd6, a GPI-tethered protein from the Ly-6/uPAR family, is expressed in the brain. It has been implicated in enhancing the Wnt/β-catenin signaling pathway and is also involved in modulating the cholinergic system [1,2]. The Wnt/β-catenin signaling is crucial during embryogenesis, tissue homeostasis, and regeneration, while the cholinergic system is important for various brain functions. Genetic models, such as knockout mice, can be valuable in studying Lypd6's functions.

In Lypd6 knockout (KO) mice, loss of Lypd6 led to decreased digging behavior in the marble burying test and increased time spent in the open area in the elevated zero maze test, indicating reduced anxiety-like behavior [4]. Also, nicotine-evoked whole-cell currents were enhanced in dorsal raphe nuclei neurons from Lypd6 KO mice, suggesting a role of Lypd6 in modulating cholinergic responses related to anxiety [4]. Overexpression of Lypd6 in the mouse brain via intracerebroventricular delivery led to memory impairment, acute stress, and down-regulation of hippocampal and amygdala dendritic spine density, as well as down-regulation of hippocampal Lypd6, Lypd6b, and α7 nicotinic acetylcholine receptor expression [3].

In conclusion, Lypd6 is an important modulator of the Wnt/β-catenin and cholinergic systems. Studies using Lypd6 KO mouse models have revealed its role in anxiety-related behaviors and cognitive functions. These findings suggest that Lypd6 may be a potential target for treating anxiety-related disorders and cognitive decline associated with its dysregulation [3,4].