Forms a proton-selective ion channel that is necessary for the efficient release of the viral genome during virus entry. After attaching to the cell surface, the virion enters the cell by endocytosis. Acidification of the endosome triggers M2 ion channel activity. The influx of protons into virion interior is believed to disrupt interactions between the viral ribonucleoprotein (RNP), matrix protein 1 (M1), and lipid bilayers, thereby freeing the viral genome from interaction with viral proteins and enabling RNA segments to migrate to the host cell nucleus, where influenza virus RNA transcription and replication occur. Also plays a role in viral proteins secretory pathway. Elevates the intravesicular pH of normally acidic compartments, such as trans-Golgi network, preventing newly formed hemagglutinin from premature switching to the fusion-active conformation. The M2 protein from most influenza A strains is inhibited by amantadine and rimantadine, resulting in viral uncoating incapacity. Emergence of amantadine-resistant variants is usually rapid. Homotetramer; composed of two disulfide-linked dimers held together by non-covalent interactions. May interact with matrix protein 1. Abundantly expressed at the apical plasma membrane in infected polarized epithelial cells, in close proximity to budding and assembled virions. Minor component of virions (only 16-20 molecules/virion). Only the first 9 residues are shared by the 2 isoforms. Cytoplasmic tail plays an important role in virion assembly and morphogenesis. When the channel is activated, one or more imidazole moieties of His-37 probably become bi-protonated. Belongs to the influenza viruses matrix protein M2 family.