<p>Inositol 1,4,5-trisphosphate kinase (IP3K) is a key regulatory enzyme within the phosphatidylinositol signaling pathway, modulating downstream signal transduction via the phosphorylation of inositol trisphosphate (IP3). Our previous comparative transcriptomic analysis of the razor clam (<i>Sinonovacula constricta</i>) under low salinity stress revealed significant enrichment of the phosphatidylinositol pathway. In this study, we characterized the <i>IP3K</i> gene and employed RNA interference (RNAi) to investigate its regulatory role by assessing downstream signaling, oxidative stress, and apoptosis under low-salinity (5 ppt) in <i>S. constricta</i>. The results showed that <i>IP3K</i> has a ubiquitous expression pattern along with significant increases in its expression in the gill under low-salinity stress. <i>IP3K</i> knockdown led to significant decreases in phosphatidylinositol (PI) and IP3 levels, altered Ca²⁺ level, and also triggered accumulation of reactive oxygen species (ROS). Concurrently, inhibition of <i>IP3K</i> significantly reduced the activities of superoxide dismutase (SOD) and catalase (CAT), while significantly increasing the content of malondialdehyde (MDA) (<i>P</i> &lt; 0.01). TUNEL staining confirmed that <i>IP3K</i> suppression exacerbated apoptosis in gill tissues, leading to a marked decline in cell viability. Overall, these findings demonstrate that <i>IP3K</i> plays an essential role in regulating oxidative stress and maintaining cellular homeostasis under low salinity conditions, providing a potential target for improving salinity tolerance in shellfish.</p>