Calcium ion (Ca2+) plays a crucial role in various physiological processes, including memory formation, cell-cell communication, and apoptosis. Maintaining an optimal concentration of Ca2+ within the cell is essential for proper cellular functioning. Disruptions in Ca2+ homeostasis can result in protein aggregation, leading to neurodegenerative disorders such as Alzheimer's and Parkinson's disease (PD). Recently, a mitochondrial microprotein called PIGBOS1 has emerged as a key regulator of the ER stress response through its interaction with an ER-resident chloride channel called CLIC-like1 (CLCC1). Suppression of either PIGBOS1 or CLCC1 individually has been shown to intensify ER stress and increase cell death. In this study, I aimed to investigate the role of PIGBOS1 in cellular Ca2+ homeostasis by monitoring Ca2+ dynamics in the ER, cytoplasm, and mitochondria using genetically encoded Ca2+ indicators. HEK-293T cells overexpressing PIGBOS1 exhibited a higher basal level of Ca2+ in the ER. Furthermore, these cells showed an increased rise in cytosolic and mitochondrial Ca2+ levels following ionomycin/histamine treatment. Collectively, these results suggest that PIGBOS1 is an integral component of the cellular Ca2+ signaling network and may have implications in the development of diseases like PD. I, therefore, plan to further study whether the calcium alterations are indirectly linked with PIGBOS1 modulating the ion channel activity of CLCC1 and to explore any potential involvement of PIGBOS1 and CLCC1 in neurodegenerative disorders.