Slc22a3, which encodes an organic cation transport protein, is critical for drug transportation, cellular detoxification, and interorgan and interorganism small-molecule communication, regulating local and overall homeostasis in the body [2,4]. It may be involved in pathways related to neurotransmitter regulation as it is a transporter for neurotransmitters like norepinephrine, epinephrine, dopamine, serotonin, and histamine [4]. Genetic models can be valuable for further exploring its functions.

In a mouse model, loss of astrocytic Slc22a3 reduced serotonin levels in astrocytes, leading to alterations in histone serotonylation, reduction of γ-aminobutyric acid (GABA) biosynthetic genes expression and GABA release, and ultimately resulting in olfactory deficits, indicating its role in sensory processing [1]. In leukemia cells, knockdown of SLC22A3 enhanced cell proliferation and suppressed cell apoptosis, suggesting its potential role in leukemia prognosis [2]. In enzalutamide-resistant castration-resistant prostate cancer cells, repression of SLC22A3 by the AR-V7/YAP1/TAZ axis conferred drug resistance [3].

In conclusion, Slc22a3 is essential for multiple biological functions including neurotransmitter-related regulation, drug transportation, and cellular detoxification. Model-based research, such as gene knockdown in cell lines or loss-of-function in mouse models, has revealed its significant roles in diseases like sensory processing disorders, leukemia, and prostate cancer resistance, providing insights into disease mechanisms and potential therapeutic targets.