In the symposium entitled “Regulation of presenilin/gamma-secretase function; towards intervention of Alzheimer disease in future” , four speakers presented new data about presenilin/gamma-secretase. Okochi and Tagami presented that toxic Aβ42 is directly cleaved into non-toxic toxic Aβ38 in living cells and analyzed the process in detail. Dr. Nishimura presented that gamma-secretase activity undergoes an age-related, non-genetic modulation through analysis of Aβ peptides in CSF of cynomolgus monkeys. Dr. Funamoto presented that gamma-secretase distinguishes the ectodomain length of substrates and that the ectodomain of C99 (the precursor of Aβ peptides) is a potent target for substrate-specific inhibition of both beta-and gamma-secretases. Dr. Tomita presented that gamma-Secretase activity is regulated by its subcellular localization, which might impact the enzymatic activity and synaptic function. Each speaker summarized their presentation below together with one figure. Okochi and Dr. Nishimura presided chair.