Proteins take center stage in directing the working of living cells. Every conceivable role within human bodies is played by proteins, from catalysis chemical reactions to defence against alien attack. A variety of quality control mechanisms that operate in the endoplasmic reticulum in downstream compart-ments of the secretary pathway to ensure the fidelity and regulation of protein expression during cell life and differentiation were introduced. The posttrans-lational quality control and its relation with protein misfolding were discussed in details. A number of diseases related with protein misfolding were introduced and the principles of therapy were discussed.