On the basis of both functional and structural considerations, members of the IκB family of proteins can be divided into four groups. The first of these groups, IκB-α, includes the avian protein pp40 and the mammalian MAD-3, both of which inhibit binding of p50-p65 NFkB complex or Rel protein to their cognate binding sites but do not inhibit the binding of p50 homodimer to κB sites, suggesting that the IκB-α family binds to the p65 subunit of p50-p65 heterocomplex through ankyrin repeats. The second member of the IκB family is represented by a protein designated IκB-β. The third group of IκB proteins is represented by IκB-γ, which is identical in sequence with the C-terminal domain of the p110 precursor of NFkB p50 and is expressed predominantly in lymphoid cells. An additional IκB family member, IκB-ε, has several phosphorylated forms and is primarily found complexed with Rel A and/or c-Rel.