SNARE and SM proteins are essential components of the intracellular membrane fusion machinery. SNARE proteins generate the force required for membrane fusion by forming a four-helix bundle that pulls membranes together. SM proteins, shaped like clasps, bind to trans-SNARE complexes to direct their fusogenic action. These proteins work together to ensure specificity and control in fusion events, particularly in synaptic exocytosis, where they are regulated by Ca²⁺-sensor synaptotagmin and clamp-activator complexin. SNARE proteins are divided into v-SNAREs (found in transport vesicles) and t-SNAREs (found in target membranes). They form trans-SNARE complexes that drive fusion by exerting mechanical force. SM proteins, such as Munc18-1, bind to t-SNAREs and help organize trans-SNARE complexes spatially and temporally. They also play a role in clamping SNARE complexes until the appropriate trigger, such as Ca²⁺, is present. Complexin and synaptotagmin are key regulatory proteins in synaptic transmission. Complexin clamps SNARE complexes, preventing premature fusion, while synaptotagmin, a Ca²⁺-sensor, triggers fusion by binding to SNARE complexes and phospholipids upon Ca²⁺ entry. This interaction allows for the precise timing of neurotransmitter release, essential for brain function. The fusion machinery is regulated by a combination of SNARE and SM proteins, ensuring that fusion occurs only when needed. This regulation is crucial for processes such as synaptic transmission, cell division, and hormone signaling. Understanding the mechanisms by which these proteins function together provides insights into the molecular basis of cellular processes and diseases associated with membrane fusion defects.SNARE and SM proteins are essential components of the intracellular membrane fusion machinery. SNARE proteins generate the force required for membrane fusion by forming a four-helix bundle that pulls membranes together. SM proteins, shaped like clasps, bind to trans-SNARE complexes to direct their fusogenic action. These proteins work together to ensure specificity and control in fusion events, particularly in synaptic exocytosis, where they are regulated by Ca²⁺-sensor synaptotagmin and clamp-activator complexin. SNARE proteins are divided into v-SNAREs (found in transport vesicles) and t-SNAREs (found in target membranes). They form trans-SNARE complexes that drive fusion by exerting mechanical force. SM proteins, such as Munc18-1, bind to t-SNAREs and help organize trans-SNARE complexes spatially and temporally. They also play a role in clamping SNARE complexes until the appropriate trigger, such as Ca²⁺, is present. Complexin and synaptotagmin are key regulatory proteins in synaptic transmission. Complexin clamps SNARE complexes, preventing premature fusion, while synaptotagmin, a Ca²⁺-sensor, triggers fusion by binding to SNARE complexes and phospholipids upon Ca²⁺ entry. This interaction allows for the precise timing of neurotransmitter release, essential for brain function. The fusion machinery is regulated by a combination of SNARE and SM proteins, ensuring that fusion occurs only when needed. This regulation is crucial for processes such as synaptic transmission, cell division, and hormone signaling. Understanding the mechanisms by which these proteins function together provides insights into the molecular basis of cellular processes and diseases associated with membrane fusion defects.