Cysticercosis is the most common helminthic disease of the nervous system in humans. The clinical presentation of neurocysticercosis (NCC) is nonspecifi c and can mimic a wide array of primary central nervous system (CNS) disorders, making its diagnosis a challenge especially in endemic areas. The pathophysiology of episodic CNS manifestations of NCC is not well understood. We support the hypothesis that mechanisms used by cysticerci to escape the host's immune system interfere with store-operated calcium entry (SOCE) pathways. This interference may modify brain excitability, leading to episodic manifestations like epilepsy and headaches. Recent fi ndings suggest that the store-operated calcium entry (SOCE) signaling pathway expressed in host tissues is downregulated by cysticerci ligands. SOCE regulates a vast array of cellular functions in excitable and non-excitable cells including modulation of neuronal excitability and regulation of synaptic plasticity. Inhibition of the SOCE signaling pathway alters synaptic plasticity and synchronization of cortical neuronal networks in vitro and in vivo. These modifi cations may lower seizure or headache thresholds, increasing the probability of developing these disorders. This hypothesis could be explored to improve our understanding of the mechanisms involved in episodic manifestations of NCC. If confi rmed, potential therapeutic opportunities could be expected from pharmacological modulations of specifi c proteins in the SOCE signaling pathway.