650 membrane proteins SUN1 and SUN2 and likely other factors implicated in nuclear positioning and nucleo-cyto- skeleton interplay, a relevant aspect in adipose tissue, skin, and bone development, which are target tissues in MADA patients. Second, improvement of the cellular phenotype by statin or statin/TSA treatment is better reached in low passage cells, when only the farnesylated form of prelamin A is accumulated. The latter ﬁnding further implies that simultaneous accumulation of different prelamin A pro- cessing intermediates might worsen the cellular phenotype and result into a less tractable pathology. Further, these data, and the evidence that drug-mediated improvement of the nuclear phenotype is also inﬂuenced by patient age at biopsy, may help explaining the efﬁcacy of current clinical trials with statins in MADA and the less satisfactory response observed in older patients. Moreover, this study shows how different protein part- ners are differently affected by drug treatments, supporting a picture of an intricate network of ﬁnely regulated inter- actions involved in pathogenetic mechanisms. In this context, the global restoration of this variety of functional interactions in which prelamin A plays a central role, appears even more complicated, raising the need of more than a univocal strategy (Richards et al. 2011) for effective treatment. Acknowledgments The technical support of P. Sabatelli, A. Val- mori, S. Grasso and D. Zini is gratefully acknowledged. This work was supported Italian MIUR PRIN 2008 to G.L., Italian Firb 2010 to N.M.M., Italian ISS ‘‘Rare diseases Italy–USA program’’ grant no. 526/D30, by a grant from ‘‘Fondazione Carisbo’’, Italy and a grant from A.I.Pro.Sa.B., Italy to G.L. and AIFA to G.N. 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