The integral membrane protein, M2, of influenza virus forms pH-gated proton channels in the viral lipid envelope. The low pH of an endosome activates the M2 channel prior to hemagglutinin-mediated fusion. Conductance of protons acidifies the viral interior and thereby facilitates dissociation of the matrix protein from the viral nucleoproteins – a required process for unpacking of the viral genome. M2 is the target of Amantadine. The M2 protein has an important role in both the early and late replication cycle of the influenza A virus. The M2 proton channel maintains pH across the viral membrane during cell entry and across the trans-Golgi membrane of infected cells during viral maturation. As virus enters the host cell by receptor mediated endocytosis, endosomal acidification occurs. This low pH activates the M2 channel. M2 now brings protons into the virion core.