Neurodegenerative disorders are highly prevalent and diverse in nature. Their manifestation largely depends on the cell types involved, with aberrant inflammatory episodes progressively inducing a constellation of phenotypes that are classified into specific diseases based on their neuropathological traits. The two most prevalent neurodegenerative diseases worldwide, Alzheimer’s disease (AD) and Parkinson’s disease (PD), for example, share notable similarities, yet they differ in terms of the specific cell types lost within the central nervous system (CNS). The significant and progressive loss of cortical and certain subcortical neurons in various regions is a major defining trait of AD. In contrast, the specific loss of dopaminergic neurons (DA) within the substantial nigra pars compacta (SNpc) is sufficient to cause motor symptoms associated with PD. Another devastating condition arising from neurodegeneration within the CNS, amyotrophic lateral sclerosis (ALS), results in the progressive death of upper and lower motor neurons. This degeneration originates in oligodendrocytes, whose defective myelination abilities lead to the denervation of the anterior horn, aggravating motor neuron death. In the case of Huntington’s disease (HD), early motor symptoms are generally attributed to the selective loss of D2-medium spiny neurons. These multifactorial diseases involve diverse risk factors and complex pathobiological mechanisms that are intertwined and convoluted. Intriguingly, a growing body of research in recent years has associated inward-rectifying potassium (Kir) channels with several neurodegenerative diseases such as AD (Akyuz et al., 2020), ALS (Peric et al., 2021), HD (Tong et al., 2014) and PD (Liu et al., 2022).