A　protein-sized　(ca.　4.2×4.2×3.6　nm3)　non-biologically　derived　molecule　{Nb288O768(OH)48(CO3)12}　(Nb288)　containing　up　to　288　niobium　atoms　has　been　obtained,　which　is　by　far　the　largest　and　the　highest　nuclearity　polyoxoniobate　(PONb).　Particularly,　in　terms　of　metal　nuclearity　number,　Nb288　is　the　second　largest　cluster　so　far　reported　in　classic　polyoxometalate　chemistry　(V,　Mo,　W,　Nb,　and　Ta).　Nb288　can　be　described　as　a　giant　windmill-like　cluster　aggregate　of　six　nanoscale　high-nuclearity　PONb　units　{Nb47O128(OH)6(CO3)2}　(Nb47)　joined　together　by　six　additional　Nb　ions.　Interestingly,　the　47-nuclearity　Nb47　units　generated　in　situ　can　be　isolated　and　bridged　by　copper　complexes　to　form　an　inorganic–organic　hybrid　three-dimensional　PONb　framework,　which　exhibits　effective　catalytic　activity　for　hydrolyzing　nerve　agent　simulant　of　dimethyl　methylphosphonate.　The　unique　Nb47　cluster　also　provides　a　new　type　of　topology　to　very　limited　family　of　Nb-O　clusters.　©　2018　Wiley-VCH　Verlag　GmbH　&　Co.　KGaA,　Weinheim