Kcnj2, encoding the α subunit of the K+ channel protein Kir2.1, is crucial for regulating potassium ion flow. It is involved in various biological processes such as maintaining the resting membrane potential in neurons and cardiomyocytes, and is associated with pathways related to cell excitability. Its function is of great biological importance as it impacts normal physiological activities in the body [2].

In a human brain organoid model of traumatic brain injury, genome-wide CRISPR interference screening (a form of functional study) identified that inhibition of Kcnj2 potently mitigated neurodegenerative processes both in vitro and in vivo, including in organoids derived from C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia patients. This suggests Kcnj2 may play a role in the neurodegenerative processes following brain injury [1].

In Andersen-Tawil Syndrome (ATS), a rare genetic multisystem channelopathy, ATS type 1 is caused by mutations in Kcnj2 (≈ 50-60% of cases), leading to a triad of periodic muscle paralysis, electrocardiogram repolarization changes, and structural body changes. Functional studies on Kcnj2 variants in patients with CPVT-like phenotypes showed that the variants act as dominant negative and drastically reduced the activity of the tetrameric channel, highlighting the importance of accurate cardiologic evaluation to distinguish atypical ATS from CPVT [2,3].

In conclusion, Kcnj2 is essential for maintaining normal cell excitability in neurons and cardiomyocytes. Model-based research, such as the use of human brain organoids and functional studies on Kcnj2 variants in ATS patients, has revealed its role in neurodegenerative processes after brain injury and in ATS. Understanding Kcnj2's function provides insights into potential therapeutic targets for these disease conditions.