Ketamine was formerly introduced as an anesthesia drug and known as a non-competitive antagonist of the N-methyl-Daspartate receptor (NMDAR). As knowledge grows, recent studies reveal the antidepressant effect of the drug. Moreover, a few investigations indicate that ketamine might be responsible for multiple calcium-regulated signaling pathways. Ketamine is thought to affect calcium homeostasis through several of its targets, such as N-Methyl-D-Aspartate (NMDA), α-amino-3-hydroxy- 5-methylisoxazole-4-propionate acid receptors (AMPA), and voltage-dependent calcium channels (VDCCs). © 2024, Legiran et al.