ULK4

ULK4 Full Name

unc-51 like kinase 4

ULK4 Introduction

ULK4 encodes a serine/threonine protein kinase belonging to the UNC-51/ATG1 family, a group of enzymes best known for orchestrating autophagy and neuronal wiring. In humans, ULK4 is expressed almost exclusively in the developing and adult brain, where it acts as a signaling hub that integrates several major pathways implicated in neurodevelopment, including ERK, p38, PKC, and JNK MAP kinase cascades. Genetic studies have repeatedly flagged ULK4 as a rare risk factor for neuropsychiatric disease: recurrent intragenic deletions spanning its exons have been found in individuals with schizophrenia, bipolar disorder, and autism spectrum disorder, while common single-nucleotide variants near the locus are associated with major depressive disorder and with the response to antipsychotic treatment. Although the gene is large and produces multiple splice isoforms, its core biochemical identity is that of a kinase whose activity helps translate extracellular developmental cues into cytoskeletal and transcriptional programs inside neurons.

Figure 1. Domain architecture of the human ULK family. (Source: Luo S, et al. 2022)

Functionally, ULK4 has emerged as a multifunctional regulator of brain construction and maintenance. Loss of the gene in mice disrupts the formation and migration of neural progenitor cells, leading to a thinner cerebral cortex and a reduced pool of intermediate progenitors, phenotypes that mirror the cortical-circuitry disturbances proposed to underlie schizophrenia. ULK4 additionally governs the assembly and function of motile cilia in the brain's ventricular system; mutant animals show disorganized ependymal cilia, obstructed cerebrospinal fluid flow, and hydrocephalus, implicating the kinase in ciliopathy-related brain disorders. More recent work links ULK4 to GABAergic signaling, anxiety-related behavior, and the myelination of axons. Together these findings paint ULK4 as a convergence point where cell motility, ciliary biology, and synaptic development meet. Its continued study offers a window into how a single kinase can, when perturbed, ripple across the entire architecture of the human brain.

Alternate Names for ULK4

ULK4; unc-51 like kinase 4; FAM7C1; REC01035; serine/threonine-protein kinase ULK4; unc-51-like kinase 4

• 1. Luo S, et al. ULK4 in Neurodevelopmental and Neuropsychiatric Disorders. Front Cell Dev Biol. 2022 Apr 12;10:873706.
  2. Hu L, et al. Ulk4, a Newly Discovered Susceptibility Gene for Schizophrenia, Regulates Corticogenesis in Mice. Front Cell Dev Biol. 2021 Jun 21;9:645368.