If thermal equilibrium means death, the asymmetric distribution of various substrates/infomation across the memebrane of the living cells is one of the impotant basis of the living system. This is created and maintaind by a number of active transporters including P-type ATPases, which mediate uphill transport a variety of substgrates, ranging from small cations to large phospholipids against their electrochemical gradient by utilizing ATP as an energy source. Employing biochemistry and structural biology, we try to elucidate how these protein molecules, which play a fundamental role in life, work at the “chemical” level.